Injectable PrEP Frequently Asked Questions – Clinical

• Time to protection is not known with certainty for any form of PrEP.
• The available evidence based on animal models suggests 95% of people will achieve protective blood levels of CAB-LA 7 days after their first injection. Fifty percent of people will achieve protective blood levels 1 day after the first injection.

For more information, see Appendix 1: “Time to onset of protection with Long-Acting Cabotegravir when used as Pre-exposure Prophylaxis”

Injection site reactions (ISR) including pain, induration and swelling are the most common side effect and are more likely with the first few injections. In HPTN 083, 75% of participants in the CAB-LA arm who received at least one injection reported injection site pain. Clinicians should counsel patients around prevention and management of ISRs. Helpful strategies may include over-the-counter pain medication taken before or soon after an injection and/or application of a warm compress or heating pad to the injection site for 15-20 minutes following the injection.

See: Apretude package insert

• Given the delay many patients will experience obtaining CAB-LA, clinicians should consider a rapid initiation of oral PrEP for any patient requesting such protection – to delay PrEP initiation in these circumstances exposes patients to ongoing risk of HIV acquisition.
• If patients or providers have concerns about tolerability of CAB-LA, an oral lead-in with oral cabotegravir is a reasonable option.
• Clinically, a lead in of oral cabotegravir is not needed to achieve adequate blood levels of CAB-LA upon initiation of injections.

• Oral cabotegravir tablets for this purpose – that is, explicitly as an HIV prevention strategy– is technically “off-label” according to the FDA package insert.
• FDA approved regimens to date for oral PrEP include generic TDF-FTC, or brand Truvada (TDF-FTC ) or Descovy (TAF-FTC)

See Appendix 2: Apretude package insert

• To cover known delays or gaps in CAB-LA of up to two months, when the patient plans to miss an injection visit but wishes to continue CAB-LA as soon as interrupting factors are resolved.

See Appendix #3 ”Continuing CAB-LA following Planned or Unplanned Missed Injections” for recommendations

• The decision to administer a shorter course of oral cabotegravir lead-in (<28 days) to assess medication tolerability is up to the provider, in consultation with the patient.

• It would be reasonable to restart daily oral PrEP (TAF-FTC or TDF-FTC) 7 days prior to the date on which the next CAB-LA injection would have been administered, were the patient to have continued injectable PrEP.

• An alternative form of PrEP should be initiated within 2 months of the final CAB-LA injection. Ideally, 7 days prior to the date on which the next CAB-LA injection would have been administered.

See Appendix 2: Apretude package insert

• Available evidence suggests that seven days after the first CAB-LA injection would be the appropriate time to stop oral TDF-FTC or TAF-FTC.

• There is a theoretical risk that if a CAB-LA patient is lost to follow-up, and experiences a very gradual waning of CAB-LA drug levels over many months (up to a year perhaps), not only is the patient at risk of acquiring HIV, but were the patient to contract HIV infection in this time period, the exposure to subtherapeutic blood levels of CAB-LA could induce drug resistance in the acquired virus – resistance to either cabotegravir, or perhaps the entire integrase inhibitor class of antiretrovirals more broadly.

• According to available data, there are no gender differences in clinical or practical concerns in the use of CAB-LA for HIV PrEP. Therefore, neither counseling messages nor prescribing practices need to be varied based on the gender of the patient/client, or whether the patient/client is at risk of HIV infection due to vaginal versus anal sex/exposure, etc.

• No.

• Not according to available data.

For reasons including patient preference, presence of gluteal implants, and management of injection site reactions (ISRs), clinicians have considered the appropriateness of administering CAB-LA at alternative anatomic sites. Data on administration of CAB-LA for PrEP in an alternative muscle group are not yet available but early pharmacokinetic data are promising. In a phase I treatment study, a single intramuscular dose of 600mg of cabotegravir and 900mg of rilpivirine administered in the in the lateral thigh achieved levels comparable to gluteal injections though a higher rate of ISRs was observed.

 See Pharmacokinetics and Tolerability of Cabotegravir and Rilpivirine Long-Acting Intramuscular Injections to the Vastus Lateralis (Lateral Thigh) Muscles of Healthy Adult Participants

Evidence suggested that oral tenofovir-based PrEP is effective in reducing risk of HIV acquisition in people who inject drugs (PWID) by an estimated 74%. (CDC) No data are yet available to support the use of injectable CAB-LA in those who inject drugs, despite the observation that an injectable agent might be preferred or more practical for use among those for whom daily pill adherence is challenging or who are unable to store oral medication. A small qualitative study found that injectable PrEP was acceptable among PWID. (Biello et al.) For PWID who also are at risk of HIV acquisition via sexual activity, oral or injectable PrEP are indicated for use.

Additional information

• No, there are no data to support varying dosage amount or frequency based on weight or BMI.
• A longer needle length should be considered for persons who weigh >30 kg to ensure the medication reaches the gluteus muscle.